Tissue-resident memory T (T-RM) cells are characterized by their surface expression of CD69 and can be subdivided in CD103+ and CD103-T-RM cells. The origin and functional characteristics of T-RM... Show moreTissue-resident memory T (T-RM) cells are characterized by their surface expression of CD69 and can be subdivided in CD103+ and CD103-T-RM cells. The origin and functional characteristics of T-RM cells in the renal allograft are largely unknown. To determine these features we studied T-RM cells in transplant nephrectomies. T-RM cells with a CD103+ and CD103-phenotype were present in all samples (n = 13) and were mainly CD8+ T cells. Of note, donor-derived T-RM cells were only detectable in renal allografts that failed in the first month after transplantation. Grafts, which failed later, mainly contained recipient derived T-RM cells. The gene expression profiles of the recipient derived CD8+ T-RM cells were studied in more detail and showed a previously described signature of tissue residence within both CD103+ and CD103-T-RM cells. All CD8+ T-RM cells had strong effector abilities through the production of IFN gamma and TNF alpha, and harboured high levels of intracellular granzyme B and low levels of perforin. In conclusion, our results demonstrate that donor and recipient T-RM cells reside in the rejected renal allograft. Over time, the donor-derived T-RM cells are replaced by recipient T-RM cells which have features that enables these cells to aggressively respond to the allograft. Show less
There is evolving interest in the use of mesenchymal stem cells (MSC) in solid organ transplantation. Pre-clinical transplantation models show efficacy of MSC in prolonging graft survival and a... Show moreThere is evolving interest in the use of mesenchymal stem cells (MSC) in solid organ transplantation. Pre-clinical transplantation models show efficacy of MSC in prolonging graft survival and a number of clinical studies are planned or underway. At a recent meeting of the MISOT consortium (MSC In Solid Organ Transplantation) the advances of these studies were evaluated and mechanisms underlying the potential effects of MSC discussed. Continued discussion is required for definition of safety and eventually efficacy endpoints for MSC therapy in solid organ transplantation. Show less
